Pulmonary fibrosis which arises after exposure to certain drugs and chemicals is an irreversible and poorly understood process. Our previous work, using mouse models of pulmonary fibrosis, indicates that the terminal amine groups of bleomycin are responsible for pulmonary fibrosis produced by this antibiotic. We plan to investigate the relationship of structure to pulmonary fibrosis by examining the effects of analogs, peptide fragments, and bithiazole-terminal groups of bleomycin on various types of lung cells (endothelial cells, alveolar type II pneumocytes, alveolar macrophages and fibroblasts) in tissue culture. We plan to explore the differences in intracellular accumulation and inactivation of the drug and test for the presence of plasma membrane receptors. By relating the structure of bleomycin to its effects, mechanisms common to drugs that produce fibrosis may be identified. Such experiments may provide a basis for modifying drug structure of altering the localization of bleomycin in lung without affecting its antitumor properties. Such information might be used to design new drugs that lack this adverse reaction. Clarification of the relationships between drug structure, binding, uptake and inactivation -- and injury to specific lung cells -- should illuminate our understanding of the process of pulmonary fibrosis.